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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Trends in the use of statins in Lithuania on 2005 – 2007 years / Statinų suvartojimo tendencijų analizė Lietuvoje 2005 – 2007 metais

Paulauskaitė, Inga 16 June 2008 (has links)
Objective: To compare statins according to the pharmacokinetic and pharmacodynamic characteristics within the drug class and to perform the comprehensive analysis of statins consumption in Lithuania between 2005 and 2007 years. Methods: MEDLINE database was searched to identify and evaluate all literature relating to pharmacokinetic and pharmacodynamic chareacteristics of statins. The statins sales data on units and wholesale prices in all Lithuanian regions over three years (2005 – 2007) were obtained from SoftDent, JSC database. Drugs were classified according to the Anatomic Therapeutic Chemical system and use was quantified in terms of defined daily doses. The consumption of statins was calculated by DDD methodology and expressed as DDD per 1.000 inhabitants per day. Expenditures were calculated using retail drug costs noted in basic price catalogue for reimbursement medicines, for each year separately. Pharmacoeconomic calculations were done according to cost minimization and reference price methodologies. Results: According to meta-analysis, Nice (2006 years) recommendations and clinical trials data statins are therapeutically equivalent medicines. The total consumption of these drugs increased from 3.9 DDD/1000 inhabitants/day in 2005 and reached the value 8.4 DDD/1000 inhabitants/day in 2007 in Lithuania, so the total consumption of statins increased by 53.6% over three years (2005 – 2007) period. Comparing with statins consumption in other countries, this meaning... [to full text] / Tikslai: Šio darbo tikslas yra palyginti statinus tarpusavyje pagal farmakokinetines ir farmakodinamines savybes bei atlikti statinų suvartojimo Lietuvoje analizę 2005 – 2007 metais. Metodai: Duomenys apie statinų farmakokinetines ir farmakodinamines savybes buvo surinkti iš MEDLINE elektroninių duomenų šaltinių. Duomenys apie statinų pardavimus vienetais ir didmeninėmis kainomis Lietuvoje per 2005 – 2007 metus gauti iš UAB SoftDent duomenų bazės. Vaistai buvo suklasifikuoti pagal anatominę terapinę cheminę (ATC) klasifikaciją. Statinų suvartojimas buvo vertinamas pagal apibrėžtos dienos dozės (DDD – daily defined dose) metodiką, o duomenys įvertinti pagal DDD skaičių, tenkantį 1000 gyventojų per vieną dieną. Išlaidos statinams buvo suskaičiuotos mažmeninėmis kainomis, remiantis kiekvienų metų kompensuojamųjų vaistų bazinių kainų kainynu. Statinų farmakoekonominei analizei atlikti buvo taikytas kainų mažinimo bei referentinės kainos nustatymo principas. Rezultatai: Remiantis metaanalizių, Nice (2006 metų) rekomendacijų ir klinikinių tyrimų duomenimis galima teigti, kad statinai prilygsta vienas kitam klinikiniu poveikiu. Bendras statinų suvartojimas padidėjo nuo 3,9 DDD/tūkstančiui gyventojų/dieną 2005 metais iki 8,4 DDD/tūkstančiui gyventojų/dieną 2007metais, taigi, per trejus metus bendras šių vaistų suvartojimas išaugo 53,6%. Palyginus su kitų šalių duomenimis, statinų suvartojimas 2007 metais Lietuvoje buvo apie 20 kartų mažesnis. Išlaidos statinams per trejus metus ( 2... [toliau žr. visą tekstą]
42

The effects of simvastatin on Staphyloccus aureus infection in endothelial cells

Horn, Mary P. January 2007 (has links)
Simvastatin, a commonly prescribed statin, has exhibited several unexpected non-cholesterol lowering benefits. For example, patients taking statins have a decreased mortality rate due to bactereamia, a systemic bacterial infection commonly caused by Staphylococcus aureus (S. aureus). To investigate statin protection during bactereamia, human umbilical vein endothelial cells (HUVEC) were pre-treated with simvastatin followed by infection with S. aureus, and infection was significantly decreased. Simvastatin inhibits the cholesterol biosynthesis pathway. Therefore, the protective effect of simvastatin may be due to isoprenoid inhibition, specifically, farnesyl pyrophosphate (Fpp) and geranylgeranyl pyrophosphate (GGpp). Fpp and GGpp prenylate small G-proteins that function in cytoskeletal rearrangement and endocytosis. When Fpp and GGpp were replenished, infection was not significantly reduced. Furthermore, when farnesyl transferase and geranylgeranyl transferase, enzymes essential to transfer isoprenoid group during prenylation, were inhibited a significant decrease in infection was observed. The data indicates that Fpp and GGpp are essential for S. aureus infection. / Department of Biology
43

Simvastatin treatment modulates the immune response, increasing the survival of mice infected with Staphylococcus aureus

Burns, Erin M. 09 May 2012 (has links)
Staphylococcus aureus, the most prevalant etiologic agent causing sepsis (a damaging inflammatory response), is traditionally cleared with antibiotics. Increased numbers of antibiotic-resistant strains mandate additional treatments to clear infections and prevent sepsis. There is evidence that suggests the lipid-lowering drug simvastatin may be beneficial for treating S. aureus infections due to its anti-inflammatory and immunomodulatory effects. In this study we pretreated 8-13 week old, male and female Balb/c and C57BL/6 mice with 1000 ng/g [BW] simvastatin in ethanol at 18 and 3 hours prior to S. aureus infection. We subsequently administered 10 mg/kg [BW] gentamicin in saline at 3, 6, 12, 24, and 48 hour timepoints. Another group of mice did not receive simvastatin treatment, and the final group received control treatments and was not infected with S. aureus. Our studies demonstrate that simvastatin may down-regulate sepsis-inducing inflammatory responses in S. aureus-infected C57BL/6 mice. / Department of Biology
44

Regulation of lipoprotein transport in the metabolic syndrome : impact of statin therapy /

Ooi, Esther M. M. January 2007 (has links)
Thesis (Ph.D.)--University of Western Australia, 2007.
45

Protein prenylation inhibitors reveal a novel role for rhoa and rhoc in trafficking of g protein-coupled receptors through recycling endosomes

Salo, Paul David. January 2007 (has links)
Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2008. / Committee Co-Chair: Hud, Nicholas; Committee Co-Chair: Radhakrishna, Harish; Committee Member: Doyle, Donald; Committee Member: Fahrni, Christoph; Committee Member: McCarty, Nael. Part of the SMARTech Electronic Thesis and Dissertation Collection.
46

Effects of oxidative stress on the expression and function of inducible nitric oxide synthase (iNOS) in cultured vascular smooth muscle cells

Bingi, Praveen Kumar January 2015 (has links)
The role of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) in atherosclerosis remains elusive. Several researchers argued whether iNOS and/or NO are pathogenic or cardio protective. The pathogenesis of atherosclerosis is complex and includes mechanisms associated with inducible nitric oxide synthase (iNOS). We have demonstrated that the expression and function of iNOS may be selectively down regulated by pro-oxidants such as antimycin A and diethyl maleate (DEM). To further explore the underlying mechanisms associated with these effects we have investigated whether antimycin A and/or DEM modulated the activation of key cellular signalling molecules associated with the induction of iNOS. Expression of p38 mitogen activated kinase (MAPK) and Akt were induced by exposure to lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Oxidative stress (OS) was induced using antimycin A, DEM and hydrogen peroxide (H2O2). All three OS inducers caused a significant generation of free radicals whereas only antimycin A and DEM generated superoxide radical (O2-). Also nitrite production and iNOS expression may be down regulated, in part; by pro-oxidants generating O2- but not hydroxyl radicals (OH-). Antimycin A and DEM concentration dependently inhibited the phosphorylation of p38 MAPK and Akt and this was restored when the cells were pre-treated with Atorvastatin whereas H2O2 was without any significant effect. Taken together, the data suggest novel actions for both pro-oxidants and atorvastatin which may have important implications in coronary artery disease where suppression of iNOS may be deleterious and maintaining its expression may be cardio-protective.
47

Regrese koronární aterosklerózy při hypolipidemické terapii / The coronary atherosclerosis regression during hypolipidemic therapy

Kovárník, Tomáš January 2012 (has links)
Background: There is no study focusing on changes of coronary atherosclerosis during dual hypolipidemic therapy with statin and ezetimibe. Methods: 107 patients with stable angina were enrolled and the final analysis was performed in 89 patients. Randomization was 1:1 to the group A (atorvastatin 80mg and ezetimibe 10mg) and to the standard group S. Treatment period was 12 months. Results: Changes of percent atheroma volume (PAV) were -0,4% in group A and + 1,4% in group S, p=0,014. Combine atherosclerosis regression (increase of lumen volume together with decrease of PAV) was found more frequent in group A (40,5%) than the group S (14,9%), p=0,007. The target LDLc level < 2mmol/l, presence of at least four of five atherosclerotic risk factors, and decrease of VCAM level were independent predictors for plaque regression. There were no significant differences in plaque composition between the two groups over the duration of the study. However during analysis the two groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. Conclusion: The dual hypolipidemic therapy starts atherosclerosis regression. Despite significant decrease of lipid levels the continuous plaque shift from fibro and fibro-fatty to necrotic with calcification...
48

NANOCÁPSULAS DE SINVASTATINA REVERTE DEFICIT DE MEMÓRIA EM RATOS

Guerino, Bruna Costabeber 12 July 2016 (has links)
Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-17T11:40:09Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_BrunaCostabeberGuerino.pdf: 1767438 bytes, checksum: 21a9128d4c5ddfc4768c4fa4fdc8325c (MD5) / Made available in DSpace on 2018-08-17T11:40:09Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_BrunaCostabeberGuerino.pdf: 1767438 bytes, checksum: 21a9128d4c5ddfc4768c4fa4fdc8325c (MD5) Previous issue date: 2016-07-12 / The statins are drugs used to treat hypercholesterolemia because their mechanism of action is to inhibit the enzyme HMG CoA reductase what is part of cholesterol biosynthesis. Studies have shown that statins have pleiotropic effects and action in the central nervous system (CNS) simvastatin (SIN) is evaluated as a prevention strategy in the treatment of neurodegenerative diseases such as Alzheimers and Parkinson’s. SIN is metabolized rapidly in the body with nonspecifically delivery to tissues. An alternative solution to these problems is to use nanocarriers that take the drugs to their target site. The nanocapsules systems are considered vectors for the administration of lipophilic substances by having a large surface area. The objective is to evaluate the effect of simvastatin nanocoated memory and type behavior anxious rats. The suspensions of simvastatin nanocapsules (NS) were produced by the interfacial deposition technique preformed polymer described by Fessi et al (1989) adapted by Venturini et al (2011). NS were characterized by dynamic light scattering (Zetasizer), Zeta potential, pH determination, drug content and encapsulation efficiency. The rats Wistar adult young (3 months, 250g-300g), midle aged (8 months, 450-500g) and adult old (12 to 13 months, 500g-700g) were from the central University vivarium Federal de Santa Maria and all procedures were performed after approval of CEUA (nº002/ 2016 protocol). First it performed a chronic treatment at the dose of 15 mg/kg or 30 mg/kg and SIN or NS rats young adults orally (v.o.) for 21 days and 30 min before testing of the inhibitory avoidance task (EI) was administered scopolamine amnesia-inducing (ESC) at a dose of 0.4 mg/kg. After this protocol was performed an acute treatment in young-adult rats with SIN or NS at a dose of 15mg/kg and 30 min before the EI test was administered i.p ESC or 75 min the other amnesic inducer ketamine (CET). The third protocol rats middle age was performed an acute treatment with SIN or NS v.o. at a dose of 15 mg/kg and the animals were evaluated for aversive memory in EI. In the last protocol adults age animal were treated chronically v.o. with SIN or NS at a dose of 15 mg/kg were evaluated in open field task, Plus Maze and EI. The results show that NS presented the particle diameter of 226.9 ± 16.4 nm, polydispersity 0.165 ± 0.04, zeta potential (mV) -8.4 ± 1.07) 6.67 ± 0.27 pH, efficiency encapsulation 77.7% and content of 85%. These parameters are in accordance with the methodology. Chronic treatment with SIN could reverse the damage caused by the ESC in memory at both doses compared to the SAL group. Acute doses of NS reverse the damage 11 caused in the memory of both the ESC and CET as compared to SAL groups. The SIN has a tendency effect not as expressive as the NS. In the acute treatment dose with NS or SIN adult-aged rats NS could be effective in reversing the natural memory loss. Since SIN had no effect. Chronic treatment with NS and SIN adults-old rats could reverse the natural loss of memory in the test of EI. There was no significant difference in locomotor and exploratory activity of animals. The adult aged treated with NS for a longer time in the open arms in elevated cross maze and the number of dips was greater than salt and SIN, indicating an anxiolytic effect of NS. We conclude that the NS has a more significant effect on acute doses and an anxiolytic effect on chronic treatment in adults-old mice. / As estatinas são fármacos utilizados no tratamento da hipercolesterolemia pois seu mecanismo de ação é diminuir a síntese da enzima HMG COA-redutase que faz parte da biossíntese do colesterol. Estudos têm mostrado que as estatinas possuem efeitos pleiotrópicos como ação no sistema nervoso central (SNC) A sinvastatina (SIN) está sendo estuda como uma estratégia de prevenção no tratamento de doenças neurodegenerativas como Alzheimer e Parkinson. Um dos problemas da SIN é que ela é rapidamente metabolizada no organismo e entregue de forma inespecífica aos tecidos. Uma alternativa para solução destes problemas é utilizar nanocarreadores que levam os fármacos ao seu sítio alvo. As nanocápsulas são sistemas considerados vetores para a administração de substâncias lipofílicas por possuírem uma grande área superficial. O objetivo do trabalho foi avaliar o efeito da sinvastatina nanoencapsulada na memória e no comportamento do tipo ansioso em ratos. As suspensões de nanocápsulas de sinvastatina (NS) foram produzidas através da técnica de deposição interfacial do polímero pré-formado descrita por Fessi e colaboradores (1989) e adaptada por Venturini e colaboradores (2011). As NS foram caracterizadas através do espalhamento de luz dinâmico (Zetasizer), potencial Zeta, determinação do pH, teor de fármaco e eficiência de encapsulação. Não foi realizado tratamento com nanocápsulas branca (NB), pois em trabalho anterior do grupo de pesquisa (ALVES, 2015), não foi observada diferença significativa entre os grupos SAL, NB e Näive. Os animais ratos Wistar adultos-jovens (3 meses, 250g-300g), ratos adultos meia idade (8 meses, 450-500g) e ratos adultos-velhos (12 a 13 meses, 500g-700g) foram provenientes do biotério central da Universidade Federal de Santa Maria e todos os procedimentos foram realizados após aprovação do Conselho de Ética do uso de animais do Centro Universitário Franciscano (CEUA) (protocolo nº002/2016). Primeiramente foi realizado um tratamento crônico na dose de 15 mg/kg ou 30 mg/kg com SIN ou NS em ratos adultos-jovens via oral (v.o.) durante 21 dias e 30 min antes do teste da tarefa da Esquiva Inibitória (EI) foi administrado o indutor amnésico escopolamina (ESC) na dose de 0,4 mg/kg. Após este protocolo foi realizado um tratamento agudo em ratos adultos-jovens com SIN ou NS na dose de 15mg/kg (v.o) e 30 min antes do teste de EI foi administrado i.p ESC e 75min o outro indutor amnésico a cetamina (CET). O terceiro protocolo foi realizado um tratamento agudo 9 com SIN ou NS v.o. na dose de 15 mg/kg e os animais foram avaliados quanto a memória aversiva na EI. No último protocolo os animais adultos-velhos foram tratados cronicamente v.o. com SIN ou NS na dose de 15 mg/kg e foram avaliados nos testes de Campo Aberto, Labirinto da Cruz Elevado e EI. As NS apresentaram o diâmetro de partícula 226,9 ± 16,4 nm, índice de polidispersão 0,165 ± 0,04, potencial zeta (mV) -8,4 ± 1,07), pH 6,67 ± 0,27, eficiência de encapsulação 77,7% e teor 85%. Estes parâmetros estão de acordo com a metodologia utilizada. O tratamento crônico com a SIN conseguiu reverter o dano na memória provocado pela ESC em ambas as doses comparado ao grupo SAL. As doses agudas de NS conseguirem o reverter o dano causado na memória tanto da ESC e CET. A SIN tem uma tendência efeito não tão expressivo quanto a NS. No tratamento de dose aguda com NS ou SIN em ratos adultos-meia idade a NS conseguiu ter efeito na reversão da perda natural da memória. Já a SIN não teve efeito. O tratamento crônico com NS e SIN nos ratos adultos-velhos conseguiu reverter a perda natural da memória no teste da EI. Não houve diferença significativa na locomoção e na atividade exploratória dos animais. Os animais tratados com NS ficaram durante mais tempo nos braços abertos no Labirinto de Cruz elevado e o número de mergulhos foi maior que o SAL e SIN indicando um efeito ansiolítico. Conclui-se que a NS possui um efeito mais expressivo em doses agudas e um efeito ansiolítico no tratamento crônico em ratos adultos-velhos.
49

PRODUÇÃO, CARACTERIZAÇÃO DE UMA NANOEMULSÃO CONTENDO SINVASTATINA E SUA AVALIAÇÃO NA EXCITOTOXICIDADE GLUTAMATÉRGICA

Moreira, Michele Pereira 31 March 2017 (has links)
Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-17T19:15:30Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_MichelePereiraMoreira.pdf: 1257282 bytes, checksum: ec3939cec40b071e77b87bd241002dab (MD5) / Made available in DSpace on 2018-08-17T19:15:30Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_MichelePereiraMoreira.pdf: 1257282 bytes, checksum: ec3939cec40b071e77b87bd241002dab (MD5) Previous issue date: 2017-03-31 / Simvastatin is used to treat hypercholesterolemia acting by inhibition of 3-hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase responsible for cholesterol synthesis. Studies carried out in humans, in animal models and in vitro observed neural damage reduction and increased glutamate uptake after simvastatin treatment. Glutamate is the major excitatory neurotransmitter in the central nervous system with crucial role in several physiological mechanisms, but at high levels it leads to cell death and participate to neurodegenerative diseases. Despite of pharmaceutical characteristics of simvastatin, as lipophilic drug that can cross cell membranes it has low bioavailability and non-specific biodistribution, simvastatin reach nervous system at low rates, limiting the pleiotropic effects described. Nanoemulsions may enhance solubility and increase biodistribution of lipophilic drugs, thus this technology can improve simvastatin performance in the neurodegenerative diseases treatment. The aim of study is producing simvastatin-loaded nanoemulsion, evaluate its physicochemical characteristics besides biological safety, and effect against glutamatergic toxicity. Blank nanoemulsion (without drug; BNE) and 1 mg/mL simvastatin nanoemulsion (SNE) were produced by spontaneous emulsification. Physicochemical characterization and stability were determined at three different temperatures (± 4 oC, ± 23 oC or ± 40 oC) for 15 days. Toxicity of formulations at 0.1 μg/mL; 1 μg/mL e 10 μg/mL was evaluated in Vero cell linage cultures and hippocampal slices from rat. Effect of formulations against glutamatergic excitotoxicity (10 mM glutamate) was evaluated at hippocampal slices from rat. All procedures with animals were previously approved by local Ethical Committee (CEUA no 05/2016). Formulation showed macroscopically homogeneous aspect and white color with Tyndall effect. Particle size was approximately 204 nm (BNE) and 139 (SNE). Zeta potential was -3 mV and -5 mV, for BNE and SNE respectively. Both of them appeared polydispersity index lower than 0.3, pH ± 6.5. Drug content was ± 1.01 mg/mL with encapsulation efficiency ± 98%. Formulations did not show any physicochemical alterations following 15 days at ± 23 oC or ± 40 oC, but simvastatin content was reduced. However, nanoemulsions exposed to ± 4 oC had constant drug content with increased particle size and polydispersity index. For all formulations, Zeta potential and pH were constant during 15 days. Cytotoxicity was no detected for all nanoemulsions. When hippocampal slices were incubated with glutamate with free simvastatin or SNE, 42% of cells were died, without effect of simvastatin. At the present work, nanoemulsions were produced efficiently, without cytotoxicity at parameters assayed. Additional studies should be performed to improve nanoemulsions stability. Simvastatin-loaded nanoemulsion or free did not show effect against glutamatergic damage evaluate in hippocampal slices from rat. / A sinvastatina é um fármaco prescrito para hipercolesterolemia, que atua inibindo a 3-metil-hidróxi-glutaril coenzima A (HMG-CoA) redutase, que controla a síntese do colesterol. Estudos em humanos e modelos in vitro e/ou animais indicam que a sinvastatina é capaz de reduzir o dano neural, e também aumentar a captação do glutamato. O glutamato é o principal neurotransmissor excitatório do sistema nervoso central, sendo fundamental em diferentes mecanismos fisiológicos, mas em altas concentrações pode induzir à morte celular e doenças neurodegenerativas. Apesar da sinvastatina ser um fármaco lipofílico e atravessar facilmente as barreiras celulares, a sua baixa biodisponibilidade e biodistribuição inespecífica fazem com que ela alcance o sistema nervoso em baixas concentrações, limitando os efeitos pleiotrópicos descritos. O uso de nanoemulsões pode aumentar a solubilidade e melhorar a biodistribuição de fármacos lipofílicos e, assim, pode melhorar o desempenho da sinvastatina no tratamento de doenças neurológicas. Portanto, o objetivo deste trabalho é preparar uma nanoemulsão contendo sinvastatina, avaliar suas características físico-químicas e de segurança, e avaliar o efeito contra a excitotoxicidade glutamatérgica. As nanoemulsões branca (NEB) ou contendo sinvastatina (NES) na concentração de 1 mg/mL foram preparadas por emulsificação espontânea. Foi realizada a caracterização físico-química e a estabilidade das formulações foi determinada em três temperaturas (±4 oC, ±23 oC ou ±40 oC), por 15 dias. A toxicidade das formulações foi avaliada nas concentrações de 0,1 μg/mL; 1 μg/mL e 10 μg/mL em células Vero e em fatias de hipocampo de ratos. A avaliação de efeito contra excitotoxicidade foi realizada nas fatias de hipocampo submetidas ao glutamato 10 mM. Os procedimentos descritos foram aprovados pela Comissão de Ética no Uso de Animais (CEUA) do Centro Universitário Franciscano (protocolo 05/2016). As formulações produzidas apresentaram-se homogêneas, de cor branca levemente azulada. O tamanho de partícula foi de aproximadamente 204 nm (NEB) e 139 nm (NES). O potencial zeta foi de -3 mV e -5 mV, para NEB e NES, respectivamente. Ambas apresentaram índice de polidispersão abaixo de 0,3, e o pH ± 6,5. O teor de fármaco encontrado em NES foi de ± 1,01 mg/mL com taxa de associação de ± 98%. As nanoemulsões não apresentaram alterações nas características físico-químicas após 15 dias de armazenamento, mantidas a ± 23 oC ou ± 40 oC, mas houve redução no teor de sinvastatina. Enquanto as nanoemulsões mantidas em ± 4 oC mantiveram o teor do fármaco, mas sofreram aumento no tamanho e índice de polidispersão. O potencial zeta e o pH mantiveram-se estáveis em todas as formulações desde o preparo até após 15 dias. Não houve indicativo de toxicidade por parte das nanoemulsões nos ensaios propostos. Nas fatias de hipocampo submetidas ao glutamato 10 mM e à sinvastatina livre ou em nanoemulsão, observou-se redução em até 42% da viabilidade, sem efeito da sinvastatina. Foi possível, no presente trabalho, produzir com sucesso nanoemulsões contendo sinvastatina, que não demonstraram toxicidade através dos parâmetros avaliados. Contudo estudos adicionais para melhorar a estabilidade deverão ser realizados. A sinvastatina livre ou em nanoemulsão, não foi capaz de reverter o dano provocado pelo glutamato no modelo proposto.
50

Estatinas como coadjuvantes nos tratamentos da doença de Chagas e leishmanioses / Statins as coadjuvant to treatment of Chagas disease and Leishmaniasis

Kelly Cristina Rodrigues 31 January 2014 (has links)
As doenças denominadas como negligenciadas têm causado nos últimos anos uma preocupação muito acentuada na comunidade científica e para as autoridades de saúde, relacionada às suas terapêuticas, no sentido de que os medicamentos existentes não se apresentam totalmente eficazes, além de determinarem efeitos colaterais extremamente elevados. Nesse perfil se encaixam a doença de Chagas e as Leishmanioses, etiologias determinadas respectivamente por Trypanosoma cruzi e parasitas do gênero Leishmania. Como proposta de encontrarmos uma alternativa para o tratamento dessas parasitoses, avaliamos o potencial terapêutico de três estatinas (sinvastatina, pravastatina e mevastatina), comercialmente encontradas para o tratamento de níveis elevados de colesterol e triglicérides, baseado no princípio de que a rota bioquímica para a formação de colesterol é semelhante à do ergosterol, componente da membrana plasmática desses protozoários. Foram realizadas avaliações in vitro e in vivo das estatinas puras e de suas associações com o benzonidazol, medicamento de referência no tratamento da doença de Chagas e com a anfotericina B, medicamento de referência no tratamento das leishmanioses, partindo do pressuposto que a substituição do benzonidazol / anfotericina B ou a diminuição de suas doses em combinação com as estatinas, atuando como coadjuvantes, pudessem auxiliar no tratamento e diminuir os efeitos colaterais provocados pela medicação. Observou-se nos ensaios com T. cruzi in vitro boa atividade antiparasitária, com valores de porcentagem de lise celular mais altos ou comparados aos encontrados para o benzonidazol, já in vivo, apenas a mevastatina apresentou redução da parasitemia em relação ao controle positivo e às outras estatinas testadas. Nos ensaios com L. braziliensis e L. major não foi observado resultado significante, tanto in vitro como in vivo, apesar de em algumas situações encontrarmos resultados próximos ao controle positivo. / Over recent years, neglected diseases has been a problem to the scientific community and health associations due the absence of total efficacy of drugs, and by their potential side effects. Chagas\' disease and Leishmaniasis - both caused respectively by Trypanosoma cruzi and by parasites the genus Leishmania fit on this profile. Aiming to find an alternative treatment of these parasitosis we evaluated the potential therapeutic of three statins (simvastatin, pravatatin, and mevastatin) which are commercially employed for treatment of high levels of cholesterol and triglycerides, based on the similarity of the biochemical route of cholesterol and ergosterol formation, being the ergosterol a component of plasmatic membrane of these protozoa. In vitro and in vivo evaluation were made by the association of these statins with benznidazole and amphotericin B used for Chagas\' disease and Leishmaniasis treatment respectively, hypothesizing that the replacement of benznidazole/amphotericin B or the reduction of the doses in combination with statins as coadjuvants could provide better treatment and side effects reduction caused by the commercial drugs. In vitro assays under T. cruzi showed significant antiparasitic activity when compared with benzonidazole to all statins. On the other hand in vivo assays showed parasitic reduction only by mevastatin when it was compared with positive control. L. braziliensis and L. major in in vivo assay didn´t show significant results despite the results have been similar to the positive control.

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